Impact of Patient Selection on Performance of an Early Rule-Out Pathway for Myocardial Infarction: From Research to the Real World

artery


Impact of Patient Selection on Performance of an
E arly rule-out pathways for myocardial infarction using high-sensitivity cardiac troponin are now recommended by international clinical guidelines. 1 Although developed in selected patients participating in research studies, these pathways are applied widely in clinical practice where the diagnostic performance and effectiveness may differ substantially. We previously demonstrated that the selection of patients for high-sensitivity cardiac troponin testing influences the apparent prevalence of myocardial infarction. 2 Here, we evaluated the impact of patient selection on the performance of the High-STEACS trial (High-Sensitivity Troponin in the Evaluation of Patients with Acute Coronary Syndrome) early rule-out pathway for myocardial infarction 3 in unselected consecutive patients in clinical practice and in selected patients consenting to participate in a research study.
Both cohorts comprised patients with suspected acute coronary syndrome presenting to emergency departments across 3 acute-care hospitals in Scotland. An electronic form embedded in practice was used to record prospectively the indication for cardiac troponin testing, symptoms, and timing of symptom onset. In the unselected cohort, data were collected in consecutive patients as part of a service evaluation in which the usual care clinician measured cardiac troponin for suspected acute coronary syndrome between June 7, 2021, and September 8, 2021. Data collection and record linkage were performed with approval from the Caldicott Guardian and the ethics committee. In the selected cohort, patients with suspected acute coronary syndrome were enrolled by researchers between June 1, 2013, and March 31, 2017, as described previously. 4 In this cohort, patients were approached between 8:00 am and 8:00 pm by research staff, and written informed consent was obtained. This study was registered (https:// www.clinicaltrials.gov; Unique identifier: NCT01852123) and approved by the ethics committee. Patients presenting with ST-segment-elevation myocardial infarction were excluded. These studies make use of multiple routine electronic health care data sources that are linked, deidentified, and held in our national safe haven that is accessible by approved individuals who have undertaken the necessary governance training.
In both cohorts, presentation and serial cardiac troponin concentrations were measured using the ARCHI-TECTSTAT high-sensitive troponin I assay (Abbott Laboratories) and sex-specific 99th percentile diagnostic thresholds applied (16 ng/L for women, 34 ng/L for men). We assessed the performance of the High-STEACS early rule-out pathway for an adjudicated diagnosis of myocardial infarction (type 1, 4b, or 4c) during the index hospital admission. Patients presenting within 2 hours of symptom onset (early presenters) underwent serial testing. Having access to the same clinical information in both cohorts, adjudication was performed independently by 2 cardiologists with consensus from a third where required, according to the Fourth Universal Definition of Myocardial Infarction. 5 The unselected and selected patient cohorts comprised 1242 (median age, 60 [interquartile range, 47-75] years, 46% women) and 1695 (median age, 61 [interquartile range, 52-73] years, 40% women) patients, respectively. Chest pain was the primary symptom in 91% (1128/1242) and 84% (1426/1695) of patients in the unselected and selected cohorts, respectively. The median time from symptom onset was 4 (interquartile range, 3-6) hours in the unselected cohort and 3 (interquartile range, 2-9) hours in the selected cohort. At presentation, cardiac troponin concentrations were elevated above the sexspecific 99th percentile in 14% (177/1242) and 15% (247/1695) of unselected and selected patients. On serial testing, concentrations were elevated in 17% (204/1242) and 19% (330/1695), respectively, but the proportion with a final diagnosis of myocardial infarction differed at 6% (74/1242) and 14% (232/1695), respectively.
After the initial cardiac troponin measurement, the High-STEACS pathway identified 54% (676/1242) of unselected patients and 36% (613/1695) of selected patients as low risk. Overall, more patients had myocardial infarction ruled out by the pathway in the unselected cohort than in the selected cohort (77% Our findings highlight that the performance of early rule-out pathways for acute myocardial infarction that have been developed in selected patient cohorts are likely to differ substantially when applied in clinical practice because of the lower prevalence of myocardial infarction. As a consequence, fewer patients are ruled in, and the positive predictive value of cardiac troponin for myocardial infarction is lower in practice. However, more patients are ruled out in clinical practice, resulting in greater efficacy of early rule-out pathways without compromising safety.

Figure. Performance of the High-STEACS early rule-out pathway for myocardial infarction in an unselected patient cohort from clinical practice (A) and in a selected patient cohort participating in a research study (B).
All patients were adjudicated according to the Fourth Universal Definition of Myocardial Infarction, and the classification of those ruled in by the pathway is given at the bottom the Figure. The pathway recommends that patients presenting within 2 hours of symptom onset have serial measurements. *Serial high-sensitivity cardiac troponin I (hs-cTNI) concentrations were not available in 130 patients in the unselected patient cohort (A) and in 17 patients in the selected patient cohort (B). High-STEACS indicates High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome; MI, type 1, 4b, or 4c myocardial infarction; NPV, negative predictive value; and PPV, positive predictive value.